Research at the Wisconsin Clinical Genetics Research Center has the objectives: (a) to collect, store, retrieve and analyze phenotypic, genealogic and epidemiologic data on genetic diseases and to speed the identification of previously undescribed genetic disorders and to establish their phenotypic spectrum and natural history; (b) to perform collaborative research on accumulated epidemiological, twin, linkage, and other data, and on the phenotypic, cytogenetic and biochemical aspects of congenital and chronic disease in order to define the genetic cause and pathogenetic mechanisms underlying human genetic disorders, and to improve means of pre- and postnatal detection, treatment and prevention of such conditions; and (c) to teach in this clinical research setting basic and medical genetics to medical and graduate students, house-officers, postdoctoral fellows and practicing physicians. Specifically this includes clinical, anatomical, pathological, biochemical, cytogenetical studies of infants and children with single major congenital malformation, malformation syndromes, newly recognized hereditary diseases, mental retardation and intersexuality. Many previously identified chromosome abnormalities are being restudied with newer techniques to determine sites of breaks and to assist with the mapping of chromosomes; several newly recognized hematologic disorders are being studied to elucidate their biochemical basis. A census and initial health survey of the total Old Order Amish population of Iowa, Wisconsin, Illinois and Missouri has been completed and several newly recognized genetic disorders in that population are being investigated. A diagnostic/etiologic study of some 1500 severely mentally retarded institutionalized patients has been completed; subgroups and newly recognized syndromes and genetic disorders are being studied in depth; detailed investigations of the cerebral palsy and multiple anomaly syndromes groups have been completed and have led to empiric recurrence risk figues of value for genetic counseling. A detailed review of the role of unstable premutations as a cause of human genetic disease is in progress. Studies of X-chromosome abnormalities, genetic disorders of reproduction and amniotic cells are continuing.